An investigational gene therapy for hemophilia A should encourage clinical scientists, developers, and biomanufacturers that adeno-associated viruses (AAVs) are suitable vehicles for “one and done” interventions. The therapy, which relies on a newly engineered AAV vector to deliver a clotting factor gene to liver cells, performed admirably in a recent clinical trial, imparting long-term expression of the clotting factor.
Earlier clinical trials with clotting factor genes delivered via AAV vectors had only fleeting success. Over time, the genes expressed less and less clotting factor. These disappointing results were thought to be at least partly due to an immune response to the AAV vector.
So, it is reasonable to suppose that the encouraging results from the recent trial have something to do with the newly engineered AAV vector. For details about this vector, please see “Hemophilia Gene Therapy Trial Achieves Sustained Clotting Factor Levels,” one of the articles in this eBook. But don’t stop there. Take the opportunity to see how the other articles in this eBook put this promising AAV vector into a broader context.
For example, the article titled “Viral Safety Testing: Keeping the Fly Out of the Ointment” covers a range of essential tasks: defining critical quality attributes, developing product-specific safety testing plans, and refining manufacturing processes. The article also discusses how the “good” (AAV vectors) can be more readily distinguished from the “bad” (adventitious viruses). Hint: Think next-generation sequencing.
Finally, this eBook includes a couple of articles that look at creative AAV vector applications. One of these articles (“Gene Therapy for a Rare Muscular Dystrophy Overcomes Earlier Roadblocks”) describes a clinical study in which a “compensatory protein therapy” using secreted proteins from AAV-transduced liver as a means of treating muscular dystrophy. In the other article (“For Genetic Transfer, Remote Control Optics Light AAV’s Way”), a system is described that transduces selected cells in culture—even single cells—by illuminating them with cell-compatible red light.
Applications of light-guided AAV technology needn’t be limited to cell cultures. According to the tech-nology’s developers, “It may also be applied for the site-specific in vivo gene delivery in fundamental research or (cancer) gene therapy. Another promising area of application would be in neurosciences.”
The story of the light-guided AAV vector and the other stories in this eBook may serve to remind readers that AAV advances seldom occur in isolation. They draw on varied technological developments, some rarefied. More important, they point to varied possibilities, none more essential than the development of life-saving treatments.